Presentation
The diagnosis of HELLP syndrome is made difficult because the presenting symptoms are vague and non-specific. Approximately 90% of patients present with viral type symptoms, malaise, nausea, and headache, and 65% complain of epigastric pain [7]. Early diagnosis of this disorder is critical to a good outcome so any woman presenting in the third trimester with these symptoms should have a complete blood cell count and liver function tests to rule it out [7].
The most common symptoms of HELLP syndrome include [8]:
- Malaise
- Nausea
- Vomiting
- Epigastric and right upper quadrant pain
- Headache
- Jaundice
- Weight gain
A majority of women with HELLP syndrome have proteinuria and hypertension, but not all [8]. About half of these patients also have periorbital, upper and lower extremity or pulmonary edema [5].
Diagnosis of HELLP syndrome is based on three criteria:
- Hemolysis
- Elevated aminotransferases
- Thrombocytopenia [3]
The physical examination in women with HELLP syndrome may be normal except for right upper quadrant tenderness which is present in about 90% of cases. Edema may also be present but is not significant because it is as common in normal pregnancies [7].
Entire Body System
- HELLP Syndrome
HELLP syndrome The red ribbon is a symbol used to raise awareness for HELLP. [en.wikipedia.org]
Anesthesia for caesarian section in patients with HELLP syndrome is a challenge. Measures should be taken during caesarian delivery to guard against the maternal and fetal complications associated with HELLP syndrome. [clinicaltrials.gov]
As with the more typical cases of Pre Eclampsia, HELLP syndrome can arise at any stage during the second half of pregnancy. The diagnosis of HELLP syndrome can be made by blood tests which examine liver enzymes, red blood cells and platelets. [aapec.org.au]
Therefore, HELLP syndrome is one of the most feared complications. [clinmedjournals.org]
- Anemia
Indirect Hyperbilirubinemia Hemolytic G6PD Drug related Autoimmune hemolytic anemia Hematoma resorption Ineffective erythropoiesis Gilbert's Direct (Conjugated) Hyperbilirubinemia Choledocholithiasis Cholecystitis Ascending cholangitis AIDS cholangiopathy [wikem.org]
Malaria may be complicated by development of thrombocytopenia, elevated liver enzymes, and/or hemolysis, which may be difficult to distinguish from HELLP (hemolytic anemia; elevated liver enzymes; low platelet count) syndrome in a pregnant patient. [ncbi.nlm.nih.gov]
Microangiopathic hemolytic anemia due to activation of fibrin formation in small blood vessels activates this response. Periportal necrosis caused by liver ischemia may lead to liver hemorrhage and rupture. [accesspediatrics.mhmedical.com]
- Weight Gain
Symptoms are variable, typically including right upper quadrant or epigastric abdominal pain, nausea, vomiting, excessive weight gain, generalized edema, hypertension, general malaise, right shoulder pain, backache, and/or headache. [orpha.net]
Symptoms may include fatigue; malaise; fluid retention and excess weight gain; headache; nausea and vomiting; pain in the upper right or middle of the abdomen; blurry vision; and rarely, nosebleed or seizures.[11434][1974] The cause of HELLP syndrome [rarediseases.org]
Check your weight each day. Weigh yourself every day before breakfast. Weight gain can be a sign of extra fluid in your body. Do not drink alcohol or smoke. Alcohol, nicotine, and other chemicals in cigarettes and cigars can increase your BP. [drugs.com]
gain Headache Nausea and vomiting that continues to get worse Pain in the upper right or mid part of the abdomen Blurry vision Nosebleed or other bleeding that will not stop easily (rare) Seizures or convulsions (rare) The main treatment is to deliver [nlm.nih.gov]
The following is a list of symptoms many women with this condition present: High blood pressure Abdominal tenderness (especially the upper right part of abdomen) Enlarged liver Fluid retention, excess weight gain, and/or swelling in the legs Nausea and [study.com]
- Fatigue
Symptoms may include fatigue; malaise; fluid retention and excess weight gain; headache; nausea and vomiting; pain in the upper right or middle of the abdomen; blurry vision; and rarely, nosebleed or seizures.[11434][1974] The cause of HELLP syndrome [rarediseases.org]
The condition is sometimes misdiagnosed as: Flu or other viral illness Gallbladder disease Hepatitis Idiopathic thrombocytopenic purpura (ITP) Lupus flare Thrombotic thrombocytopenic purpura Symptoms include: Fatigue or feeling unwell Fluid retention [nlm.nih.gov]
Fatigue. Nausea and vomiting. Seizure. HELLP syndrome can be life-threatening for both the mother and her fetus. A woman with symptoms of HELLP syndrome requires emergency medical treatment. [myhealth.alberta.ca]
Respiratoric
- Respiratory Distress
New symptoms of APS, including deep vein thrombosis and ischemic nervus opticus lesion, developed in the patient followed by the onset of acute respiratory distress syndrome, which required respiratory therapy. [ncbi.nlm.nih.gov]
Respiratory distress syndrome (74.4%) was the main indication for NICU admission. Perinatal mortality rate was 8.3% and neonatal mortality rate was 11.6%. Maternal morbidity rate was 30%. [doi.org]
Gastrointestinal
- Nausea
Patients manifesting this syndrome usually are seen before term (less than 36 weeks' gestation) complaining of malaise (90%), epigastric or right upper-quadrant pain (90%), and nausea or vomiting (50%), and some will have nonspecific viral-syndrome-like [ncbi.nlm.nih.gov]
Topic Snapshot A 35-year-old G4P3 at 35 weeks gestation presents to the emergency room with nausea, vomiting, and right upper quadrant pain. She has a history of pre-eclampsia in her previous pregnancy. [step2.medbullets.com]
- Vomiting
There may also be heartburn, vomiting and headache. [aapec.org.au]
Patients manifesting this syndrome usually are seen before term (less than 36 weeks' gestation) complaining of malaise (90%), epigastric or right upper-quadrant pain (90%), and nausea or vomiting (50%), and some will have nonspecific viral-syndrome-like [ncbi.nlm.nih.gov]
Topic Snapshot A 35-year-old G4P3 at 35 weeks gestation presents to the emergency room with nausea, vomiting, and right upper quadrant pain. She has a history of pre-eclampsia in her previous pregnancy. [step2.medbullets.com]
- Abdominal Pain
The upper abdominal pain of the HELLP syndrome can be very severe, and is not relieved by simple remedies such as antacids, which would be the case if heartburn, for example, was the cause of the pain. [aapec.org.au]
The most frequent signs and symptoms of hepatic rupture were the sudden onset of abdominal pain, acute anemia, and hypotension. Laboratory findings included low platelet count and increased hepatic enzymes. Surgery was performed in 9 cases. [ncbi.nlm.nih.gov]
- Epigastric Pain
We recommend that severely ill patients with HELLP syndrome having epigastric pain should undergo CT imaging of the liver. [ncbi.nlm.nih.gov]
For such patients, it was observed that those with epigastric pain, headache, phosphenes, and tinnitus had over 2, 5 times more possibilities to have LDH above 600 IU/l. [clinmedjournals.org]
- Upper Abdominal Pain
The upper abdominal pain of the HELLP syndrome can be very severe, and is not relieved by simple remedies such as antacids, which would be the case if heartburn, for example, was the cause of the pain. [aapec.org.au]
On day 2 postoperatively, she developed a sudden severe colicky upper abdominal pain with tachypnoea, dyspnoea, and tachycardia, and blood pressure (BP) reaching 150/95 mmHg. [ncbi.nlm.nih.gov]
Should be considered in any pregnant patient presenting in the second half of gestation or immediately postpartum with significant new-onset epigastric/upper abdominal pain until proven otherwise. [bestpractice.bmj.com]
Cardiovascular
- Hypertension
Severe systolic hypertension (≥160 mm Hg), severe diastolic hypertension (≥110 mm Hg), and hypertensive encephalopathy were significantly more common among women with HELLP than among those with eclampsia alone (P=0.01 for all). [ncbi.nlm.nih.gov]
However, it could be found in a small percentage in non- hypertensive obstetric patients [1]. [clinmedjournals.org]
In most cases, the detachment occurs concomitantly with hypertensive retinopathy [5]. [clinical-medicine.panafrican-med-journal.com]
It confirms the idea that PHS can occur among women with gestational hypertension or gestational hypertension superimposed upon chronic hypertension. [scielo.br]
Eyes
- Scotoma
In patients who are suffering a recurrence of preeclampsia, findings on physical examination may include the following (see Prognosis): Altered mental status Decreased vision or scotomas Papilledema Epigastric or right upper quadrant abdominal tenderness [emedicine.com]
Skin
- Purpura
CONCLUSION: Thrombotic thrombocytopenic purpura can mimic HELLP syndrome late in gestation. [ncbi.nlm.nih.gov]
The condition is sometimes misdiagnosed as: Flu or other viral illness Gallbladder disease Hepatitis Idiopathic thrombocytopenic purpura (ITP) Lupus flare Thrombotic thrombocytopenic purpura Symptoms include: Fatigue or feeling unwell Fluid retention [nlm.nih.gov]
Some women may have easy bruising/purpura. On examination, oedema, hypertension and proteinuria are present. Tenderness over the liver can occur. [patient.info]
May, Thrombotic thrombocytopenic purpura in 166 pregnancies: 1955-2006, American Journal of Obstetrics and Gynecology, 199, 2, (98), (2008). [doi.org]
- Erythema
In early lesions, as was shown in this case, a neutrophilic subcutaneous infiltrate raises a differential diagnosis including infection, subcutaneous Sweet's syndrome or atypical erythema nodosum. [ncbi.nlm.nih.gov]
Urogenital
- Cesarean Section
Approximately 8 hours after the cesarean section, she developed seizures, followed by evident acute heart and renal failure. [ncbi.nlm.nih.gov]
- Oliguria
Monitor for remission. [22] Consider steroids for up to 2 days postpartum to prevent rebound of liver dysfunction, thrombocytopenia, and oliguria. [2] Rahman TM, Wendon J. Severe hepatic dysfunction in pregnancy. [emedicine.medscape.com]
Dexamethasone treatment did not reduce maternal complications (such as acute renal failure, pulmonary oedema and oliguria). [ncbi.nlm.nih.gov]
Women with HELLP syndrome whose hypertension is controlled, oliguria responds to fluid management, and have no right upper quadrant or epigastric pain may be eligible for conservative management. [symptoma.com]
Neurologic
- Headache
[…] the studies by Tijerino, et al. [8] and Otero [15], whose main symptom was a headache. [clinmedjournals.org]
There may also be heartburn, vomiting and headache. [aapec.org.au]
The wide overlap in symptoms (headache, malaise, digestive symptoms) does not suggest that symptoms would be effective in differentiating malaria and preeclampsia. [ncbi.nlm.nih.gov]
It is clinical characterized by gradual but marked onset of headaches (30%), blurred vision, paresthesia, and hypertension (which can be mild). [accesspediatrics.mhmedical.com]
- Seizure
If needed, women are first treated with drugs to lower blood pressure (antihypertensives) and drugs to control seizures. [merckmanuals.com]
We present a rare case of HELLP syndrome which presented with ICH and further complicated by seizures, disseminated intravascular coagulation, and acute renal failure. [ncbi.nlm.nih.gov]
Magnesium is given to prevent seizures, just as it is in preeclampsia/eclampsia. [straightanursingstudent.com]
You may also receive: A blood transfusion if bleeding problems become severe Corticosteroid medicines to help the baby's lungs develop faster Medicines to treat high blood pressure Magnesium sulfate infusion to prevent seizures Outcomes are most often [nlm.nih.gov]
Workup
The platelet count is the most reliable indicator of HELLP syndrome. The D-dimer test may be a useful tool for the early identification of patients with preeclampsia who may develop severe HELLP syndrome [7].
In any pregnant woman, HELLP syndrome should be suspected with a significant drop in the platelet count. A positive D-dimer test in patients with preeclampsia has been seen to indicate those who will develop HELLP syndrome as it is a more sensitive to subclinical coagulopathy [7].
Laboratory studies should include [3]:
- Complete blood cell (CBC) count
- Coagulation studies
- Peripheral smear for schistocytes, helmet cells, burr cells
- Liver function tests: serum aspartate aminotransferase, alanine aminotransferase (AST/ALT) levels
- Lactate dehydrogenase (LDH) level
- Complete metabolic panel
- Bilirubin level
- Haptoglobin level
- Fibrinogen levels
Imaging studies are only recommended when severe liver involvement is suspected by worsening liver function tests. In this case computed tomography, magnetic resonance imaging, or hepatic ultrasound are suggested [3] [7].
Serum
- Thrombocytopenia
[…] suggestive of hemolysis (total serum LDH ≥600 IU/l); class 2 requires similar criteria except thrombocytopenia is moderate (>50,000 to ≤100,000/μl); and class 3 includes patients with mild thrombocytopenia (platelets >100,000 but ≤150,000/μl), mild hepatic [clinicaltrials.gov]
Thrombocytopenia, which is the earliest coagulopathy present in all HELLP syndrome patients, is indicated by low platelet count (below 100 x 109 L-1) or by testing the levels of fibrin metabolites and antithrombin III. [en.wikipedia.org]
Recognition of this syndrome in women with preeclampsia is increasing because of the frequency of blood test results that reveal unexpected thrombocytopenia or elevated liver enzymes. [ncbi.nlm.nih.gov]
The present study was the first to define a unifying diagnosis of HELLP syndrome as elevated blood pressures, thrombocytopenia, hemolysis, and liver dysfunction in pregnancy. [2minutemedicine.com]
- Decreased Platelet Count
Despite considerable patient variation, most gravid women with HELLP syndrome had decreasing platelet counts until 24 to 48 hours after delivery. Conversely, lactate dehydrogenase concentrations usually peaked 24 to 48 hours post partum. [ncbi.nlm.nih.gov]
TMA include thrombocytopenia (platelet count below 150,000 or a decrease from baseline of at least 25%) [15] and evidence of microangiopathic hemolysis, which is characterized by elevated LDH levels, decreased haptoglobin, decreased hemoglobin, and/or [en.wikipedia.org]
On the 2nd day after cesarean section, liver enzymes decreased, platelet count increased, and this provided us with further evidence for the diagnosis of HELLP Syndrome, although not conclusive. [dovepress.com]
- Liver Function Tests Abnormal
Hypertension-induced hepatic disease is a common cause of abdominal pain and liver function test abnormalities in the pregnant patient. [ncbi.nlm.nih.gov]
Treatment
Early diagnosis and treatment is critical in the management of HELLP syndrome as delayed intervention increases the mortality and morbidity rates significantly. Maternal mortality rate have been reported to be as high as 25% [3] [7].
The foundation of optimal treatment of HELLP syndrome is supportive care, including seizure prevention and blood pressure control [1]. Women at term should be delivered as soon as possible. Those at less than 34 weeks should be managed conservatively [7]. Severe HELLP syndrome is progressive and sudden maternal deterioration can occur. Delivery is the only effective treatment therapy [3] [8].
Stabilization and initial treatment of HELLP syndrome involve:
- Treatment to prevent seizures usually includes intravenous magnesium sulfate with a 4 to 6g loading dose over 20 minutes and then 2g per hour as maintenance. This should be continued until 24 hours after delivery [7].
- Treatment of hypertension: The goal is to keep the systolic blood pressure <160 and the diastolic blood pressure <105. Labetalol and hydralazine are the recommended drugs. Dosing for intravenous hydralazine (Apresoline) is initial small incremental doses of 2.5 to 5mg every 15 to 20 minutes until blood pressure is normal [7].
- Corticosteroid therapy is controversial [8]. It is theorized that steroid usage may decrease intravascular endothelial injury and prevent further hepatic and platelet dysfunction [3] [7]. Research has shown improvement in blood pressure, urine output, platelet count, and liver function tests [7].
- Corticosteroid therapy may also decrease fetal morbidity by reducing respiratory distress syndrome and cerebral hemorrhage [3] [6].
Patients should be monitored closely once they are stabilized. This is done best in the labor and delivery department of a tertiary health center [5] [8]. Patients close to 34 weeks gestation who have no clinical or laboratory improvement may require immediate delivery [8].
Women with HELLP syndrome whose hypertension is controlled, oliguria responds to fluid management, and have no right upper quadrant or epigastric pain may be eligible for conservative management [7].
Treatment for unstable HELLP syndrome [3] [5] [7]:
- Postpartum curettage may lower arterial pressure and improve urine output and thrombocytopenia.
- Transfusion to correct of coagulation abnormalities with plasma or platelets.
The treatment approach is different for each patient and should be based on the estimated gestational age and the condition of the mother and fetus [7].
Prognosis
Symptoms of HELLP syndrome usually resolve rapidly within 24-48 hours of delivery with normal platelet counts by 5 days [3] [5].
Persistence of hemolysis for longer than 72 hours, increasing hepatic or renal failure indicates the potential for life-threatening complications. These require further treatment such as: plasmapheresis, plasma volume expansion, antithrombotic agents, plasma exchange, transfusion, or dialysis [3].
Maternal complications, including disseminated intravascular coagulation, placental abruption and acute renal failure, are common and potentially life-threatening [6] [7].
The recurrence rate of HELLP syndrome with subsequent pregnancies is 2%-27% [7]. Patients also have an increased risk of preeclampsia or pregnancy-induced hypertension, preterm delivery, and placental abruption in future pregnancies [7].
Early diagnosis and treatment ensures the best maternal and perinatal outcomes [6] [9].
Etiology
HELLP syndrome was identified in the early 20th century as a subtype of preeclampsia [4]. In 1982 the acronym HELLP was used to describe the primary characteristics of hemolysis, elevated liver enzyme levels and low platelet count [1] [6] [3]. The cause of HELLP syndrome is unknown, although multiple theories have been advanced. HELLP syndrome is a microangiopathic hemolytic anemia resulting in small, diffuse areas of hemorrhage [3].
Risk factors for HELLP syndrome include the following [4] [7]:
- Maternal age older than 34 years
- Multiparity
- White race or European descent
- History of poor pregnancy outcome [4]
Maternal mortality rates have been reported to be as high as 25% and are dependent on time of diagnosis, maternal health, and availability of advanced medical care [8]. Cerebral hemorrhage is the most common cause of death [8].
Complications of HELLP syndrome include the following [8]:
- Disseminated intravascular coagulation (DIC) (20%)
- Placental abruption (16%)
- Acute renal failure (7%)
- Pulmonary edema (6%)
Fetal morbidity and mortality rates range from 9% to 24% [8]. The usually cause are placental abruption, intrauterine asphyxia, or prematurity [2]. The early diagnosis and treatment of HELLP syndrome is difficult due to the vague, nonspecific signs and symptoms of this disorder [9].
Epidemiology
HELLP syndrome is rare, occurring in approximately 0.1% to 0.6% of all pregnancies. The incidence is higher in patients with preeclampsia occurring in 4%-12% of these patients [6] [7].
HELLP syndrome occurs in weeks 22 to 27, at delivery, or immediately postpartum in 15%-30% of cases [3] [6].
The incidence of HELLP syndrome is significantly higher in Caucasians of European descent and women older than 25 years of age. [3]
Mortality rates [6] [3]:
- Maternal mortality 1%–25%
- Fetal/perinatal mortality 11%
Recurrence in subsequent pregnancies is 4%–19% [7].
Pathophysiology
The pathology of HELLP syndrome is not well understood. Symptoms of this multisystem disease are a result of abnormal vascular tone, vasospasm and altered coagulation [7] No common precipitating factor has been determined however. Whatever the trigger, it leads to microvascular endothelial injury and platelet activation with the release of thromboxane A and serotonin. This causes a cascade of vasospasm, platelet agglutination, and further endothelial damage [7] [10]. The process only stops with delivery [7].
HELLP syndrome involves a hemolytic anemia where red blood cells destroyed by the small damaged blood vessels. Elevated liver enzyme levels are secondary to obstruction of hepatic blood flow, liver damage, intrahepatic hemorrhage, or possible hepatic rupture [5] [7] [11]. The thrombocytopenia has been attributed to increased consumption and/or destruction of platelets [7].
Many theories have been proposed to explain the pathogenesis, but the true pathology is unknown. One theory regarding the cause of HELLP syndrome is that it is a form of severe preeclampsia, and the pathophysiology is the same. It postulates that there is a release various placental factors due to inadequate placental perfusion during the 16-22 week of pregnancy [5] [12]. This results in hypertension, proteinuria, and increased platelet depletion [13].
Another theory proposes that HELLP syndrome results from the alteration of the maternal-fetal immune balance, causing the symptoms of the disorder [14]. This suggests an inflammatory response targeting the liver [10] [12].
Complications of HELLP syndrome for the mother include [2]:
- Disseminated intravascular coagulation, bleeding, hematoma
- Cardiac arrest, myocardial ischemia
- Pulmonary edema, respiratory failure, pulmonary embolism, adult respiratory distress syndrome
- Hemorrhage/stroke, cerebral edema, central venous thrombosis, seizures, retinal detachment
- Acute renal failure, chronic renal failure requiring dialysis
- Hepatic hematoma, ascites, diabetes insipidus
- Infection
Complications for the neonate resulting from HELLP syndrome [2]:
- Prematurity
- Intrauterine growth retardation (39%)
- Thrombocytopenia
Prevention
There is currently no known means of preventing HELLP syndrome. However, early recognition and treatment of this disorder with a multidisciplinary approach can reduce maternal and perinatal morbidity and mortality [1] [4].
Summary
HELLP syndrome is a serious, potentially life-threatening, complication of pregnancy [1] [2]. It is characterized by: (H) hemolysis, (EL) elevated liver enzyme levels, and (LP) low platelet levels [2] [3]. These symptoms give the disorder its name. HELLP syndrome has been associated with poor maternal and neonatal outcomes [2].
Those at highest risk of HELLP syndrome are white, multiparous women over 25 years of age with a poor past pregnancy history. It occurs most often between 27 and 37 weeks gestation [1] [4] [5].
The clinical presentation of HELLP syndrome is often vague leading to initial misdiagnosis and delayed treatment [5] [6]. Patients may present with viral type symptoms, malaise, nausea, vomiting, and headache. Complaints of epigastric or right upper quadrant pain should alert healthcare providers to the possible diagnosis of HELLP syndrome [6].
It is theorized that HELLP is a severe form of preeclampsia. However, while preeclampsia is characterized by gestational hypertension with proteinuria, these symptoms are not always present in HELLP syndrome [1]. Another theory is that HELLP syndrome is a separate disorder [7].
The cause of HELLP syndrome is unknown and there is no known means of prevention [1].
Patient Information
What is HELLP syndrome?
HELLP syndrome is a serious, often life-threatening complication of pregnancy. Its name comes from the three primary features of the disorder: Hemolysis (destruction of red blood cells), Elevated Liver enzymes, and Low Platelet count. HELLP syndrome can result in maternal and fetal morbidity and mortality. It needs to be identified and treated early for the best prognosis.
What are the symptoms of HELLP syndrome?
The symptoms of HELLP syndrome are vague and non-specific making diagnosis difficult. Symptoms include:
- Flu-like symptoms
- Malaise
- Nausea
- Vomiting
- Epigastric and right upper quadrant pain
- Headache
- Jaundice
- Weight gain
- Hypertension and protein in the urine occur in many patients
What causes HELLP syndrome?
The cause of HELLP syndrome is not known. It is believed to be related to preeclampsia and eclampsia. Symptoms are the result of injury to the lining of the blood vessels with accumulation of platelets. The damaged vessels cause destruction of red blood cells and interrupted blood flow to the liver and kidneys.
Who gets HELLP syndrome?
HELLP syndrome occurs most frequently in Caucasian women, over the age of 25, in their third trimester of pregnancy. Those women who have preeclampsia or who have had previous problem pregnancies are at higher risk.
How is HELLP syndrome diagnosed?
There is no specific diagnostic testing for HELLP syndrome. However, any woman with the above symptoms and a low platelet count and abnormal liver function tests should be further evaluated for the disorder.
How is it treated?
The only truly effective means of treating HELLP syndrome is delivery as soon as possible. Patients must first be stabilized by controlling associated hypertension and preventing the complication of seizures. Pre-term pregnancies may be treated conservatively with antiseizure and antihypertensive medications. Corticosteroids may also be effective in controlling maternal symptoms and complication of fetal immaturity.
What are the complications?
The complications of HELLP syndrome include:
For the mother:
- Acute bleeding and hematomas
- Lung edema
- Hemorrhage/stroke
- Heart failure
- Seizures
- Kidney failure
- Liver hematoma
Complications for the neonate:
- Prematurity
- Low birth weight
- Increased risk of bleeding
How can HELLP syndrome be prevented?
There is currently no known means of preventing HELLP syndrome. However, early recognition and treatment of this disorder with a multidisciplinary approach can reduce maternal and perinatal morbidity and mortality.
References
- Weinstein L. Syndrome of hemolysis, elevated liver enzymes, and low platelet count: A severe consequence of hypertension in pregnancy. Am J Obstet Gynecol. 1982;142:159.
- Harms K, Rath W, Herting E, Kuhn W. Maternal hemolysis, elevated liver enzymes, low platelet count, and neonatal outcome. Am J Perinatol. 1995;12:1-5.
- Hay JE. Liver Disease in Pregnancy. Hepatology. 2008; 47(3): 1067-77.
- Rahman TM, Wendon J. Severe hepatic dysfunction in pregnancy. Quart J Med. 2002;95:343-352.
- Mutter WP, Karumanchi SA. Molecular mechanisms of preeclampsia. Microvasc Res. 2008;75:1-8.
- Geary M. The HELLP syndrome. Br J Obstet Gynaecol. 1997;104, 887-891.
- Ohara Padden, M. HELLP Syndrome: Recognition and Perinatal Management. Am Fam Physician. 1999;60(3):829-836.
- Barton JR, Sibai BM. Diagnosis and management of hemolysis, elevated liver enzymes, and low platelets syndrome. Clin Perinatol. 2004;31:807-33.
- Magann EF, Martin JN Jr. Twelve steps to optimal management of HELLP syndrome. Clin Obstet Gynecol. 1999;42:532-538.
- Fang CJ, Richards A, Liszewski MK, Kavanagh D, Atkinson JP. Advances in understanding of pathogenesis of aHUS and HELLP. British Journal of Haematology. 2008;143: 336–348.
- Widmer M, Villar J, Beniani A, et al. Mapping the theories of preeclampsia and the role of angiogenic factors: A systematic review. Obstet Gynecol. 2007;109:168-173.
- Hulstein JJ, van Runnard HPJ, Franx A, Lenting PJ, Bruinse HW, Silence K, et al. Acute activation of the endothelium results in increased levels of active von Willebrand factor in hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome. J Thromb Haemost. 2006; 4: 2569–75.
- Gyselaers W, Mullens W, Tomsin K, Mesens T, Peeters L. Role of dysfunctional maternal venous hemodynamics in the pathophysiology of pre-eclampsia: a review Ultrasound Obstet Gynecol. 2011; 38: 123–129.
- Hulstein JJJ, Van Runnard Heimel PJ, Franx A, . Lenting PJ, Bruinse HW, Silence K, et al. Vascular endothelial growth factor ligands and receptors that regulate human cytotrophoblast survival are dysregulated in severe preeclampsia and hemolysis, elevated liver enzymes, and low platelets syndrome. Am J Pathol. 2002;160:1405-23.